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Structural basis of gating of CNG channels
Authors:Giorgetti Alejandro  Nair Anil V  Codega Paolo  Torre Vincent  Carloni Paolo
Affiliation:Istituto Nazionale per la Fisica della Materia and International School for Advanced Studies, Via Beirut 4, 34014 Trieste, Italy.
Abstract:Cyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5A thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed.
Keywords:CNG channels   Gating mechanism   Comparative modelling   Structural basis   Distance restraints
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